Faculty, Staff and Student Publications
Publication Date
2-20-2025
Journal
The Journal of Infectious Diseases
Abstract
Enterococci have evolved resistance mechanisms to protect their cell envelopes against bacteriocins and host cationic antimicrobial peptides (CAMPs) produced in the gastrointestinal environment. Activation of the membrane stress response has also been tied to resistance to the lipopeptide antibiotic daptomycin. However, the actual effectors mediating resistance have not been elucidated. Here, we show that the MadRS (formerly YxdJK) membrane antimicrobial peptide defense system controls a network of genes, including a previously uncharacterized 3-gene operon (madEFG) that protects the Enterococcus faecalis cell envelope from antimicrobial peptides. Constitutive activation of the system confers protection against CAMPs and daptomycin in the absence of a functional LiaFSR system and leads to persistence of cardiac microlesions in vivo. Moreover, changes in the lipid cell membrane environment alter CAMP susceptibility and expression of the MadRS system. Thus, we provide a framework supporting a multilayered envelope defense mechanism for resistance and survival coupled to virulence.
Keywords
Enterococcus faecalis, Anti-Bacterial Agents, Signal Transduction, Antimicrobial Peptides, Membrane Lipids, Cell Membrane, Drug Resistance, Bacterial, Antimicrobial Cationic Peptides, Animals, Bacterial Proteins, Gene Expression Regulation, Bacterial, Daptomycin, Stress, Physiological, Mice, Gram-Positive Bacterial Infections, Enterococcus faecalis, daptomycin, antimicrobial peptides, membrane lipids, cell envelope stress response
DOI
10.1093/infdis/jiae173
PMID
38578967
PMCID
PMC11841629
PubMedCentral® Posted Date
4-5-2024
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes